The overall objectives of the project reflect our interest in the interaction of nitrosourea anti-tumor agents on chromatin and specifically transcriptionally active chromatin in mammalian cells. The anticipated goals for the current year include: 1. Determination of the relative sites of alkylation and carbamoylation of nitrosoureas to the histone-free versus histone-protective regions of nucleosomal chromatin. 2. Identification of the species of nuclear proteins modified within the above regions of nucleosomal chromatin. 3. Evaluation of the influence of butyric acid-induced differentiation in cells as it relates to nitrosourea interaction with chromatin. 4. A survey of the effect of various hormones on mammalian cells in culture with aims towards investigating whether euchromatin regions in nuclei are selected targets for interaction with nitrosoureas. 5. Evaluation of effect of amino acid deprivation of eukaryotic cells on the differential interaction of nitrosoureas with chromatin subparticles and transcriptionally active chromatin species.